A meta-analysis of data from several randomized, controlled studies in patients with atrial flutter and fibrillation indicates that quinidine therapy may be associated with a mortality rate >3 times higher than that associated with placebo.163167168169170

A meta-analysis in patients with various non-life-threatening ventricular arrhythmias showed mortality associated with quinidine was consistently greater than that associated with various other antiarrhythmic agents (i.e., flecainide, mexiletine, propafenone, tocainide).163167168169170

Introduction

Uses for Quinidine Gluconate

Comparably effective to procainamide for atrial or ventricular arrhythmias; choice based on pharmacokinetics and adverse effect profile.b

Supraventricular Tachyarrhythmias

Used for conversion of atrial fibrillation or flutter in patients whose symptoms are not adequately controlled by measures to reduce ventricular rate; also may be used to maintain normal sinus rhythm after conversion.119163167169170301 However, used infrequently because of adverse effects (e.g., QT-interval prolongation, torsades de pointes, increased mortality) and considered an alternative to other antiarrhythmic agents.301

Has been used for treatment of other supraventricular tachycardias (e.g., paroxysmal atrial tachycardia, paroxysmal AV junctional rhythm); however, other therapies preferred.300b

Ventricular Arrhythmias

Suppression and prevention of recurrent ventricular arrhythmias (e.g., sustained VT) that in the judgment of the clinician are life-threatening.b Because of arrhythmogenic potential and lack of evidence for improved survival for class I antiarrhythmic agents,146147not recommended for less severe arrhythmias; avoid treatment in asymptomatic VPCs.b (See Boxed Warning.)

Parenteral lidocaine is considered drug of choice for treatment of VPCs because quinidine can decrease myocardial contractility.b

Like other antiarrhythmic drugs, not shown to decrease mortality rate in VPCs associated with acute MI.b

Malaria

Severe malaria usually caused by P. falciparum;143144P. knowlesi also can cause severe disease.143 Can be rapidly progressive and fatal (most deaths occur within first 24–48 hours of illness);143 initial aggressive treatment with a parenteral antimalarial regimen indicated as soon as possible after diagnosis (regardless of Plasmodium species involved) and whenever suspected based on possible exposure and symptoms.143144

For initial treatment of severe malaria in adults or children, CDC recommends a regimen of IV quinidine gluconate in conjunction with doxycycline, tetracycline, or clindamycin (oral or IV as tolerated).143144 After at least 24 hours and when parasitemia is reduced to <1% and an oral regimen can be tolerated, IV quinidine gluconate can be discontinued and oral quinine sulfate initiated to complete 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).143144 Oral antimalarials not recommended for initial treatment of severe malaria.143

Because of potentially fatal consequences of delays in initiating treatment of severe malaria, institutional pharmacy services should be aware of the essential role of ready availability of IV quinidine gluconate.142143148153 (See Availability for Use in Treatment of Severe Malaria under Cautions.)

If IV quinidine gluconate is unavailable locally and cannot be obtained quickly or cannot be used because of adverse effects or contraindications or if parasitemia is high and has not responded to quinidine gluconate, IV artesunate is available from CDC under an investigational new drug (IND) protocol for initial treatment of severe malaria.143144171172 WHO recommends IV artesunate as the drug of choice for treatment of severe malaria.161

Although oral quinidine sulfate has been used for treatment of malaria,167170 including uncomplicated malaria† caused by multidrug-resistant P. falciparum,102104108109110112 oral quinine sulfate is not included in CDC recommendations for treatment of uncomplicated or severe P. falciparum malaria.143144

Assistance with diagnosis or treatment of malaria or assistance obtaining IV quinidine gluconate or IV artesunate for treatment of severe malaria is available by contacting CDC Malaria Hotline at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143144171172

Quinidine Gluconate Dosage and Administration

General

Arrhythmias

Initiate quinidine or adjust quinidine dosage in a setting where facilities and personnel for patient monitoring and resuscitation are continuously available, especially if used in patients with known structural heart disease or other risk factors for toxicity.163167168169170

ECG monitoring of cardiac function and determination of plasma concentrations are recommended, especially when given IV or when >2 g is administered orally daily, and in patients with an increased risk of adverse reactions to quinidine (e.g., severe heart disease, hypotension, hepatic or renal disease).b

Use for conversion of atrial fibrillation/flutter only after alternative measures (e.g., use of other drugs to control ventricular rate) have been inadequate.163167168169170 Discontinue quinidine if sinus rhythm is not restored within a reasonable amount of time.119163167168169170

Discontinue quinidine and consider other means of conversion if QRS complex widens to 130% of its pretreatment duration, QTc interval widens to 130% of its pretreatment duration and is >500 milliseconds, P waves disappear, or patient develops clinically important tachycardia, symptomatic bradycardia, or hypotension.119163167168169170

Malaria

Initiate IV quinidine gluconate regimen as soon as possible after severe malaria diagnosed (regardless of Plasmodium species involved) and whenever suspected based on possible exposure and symptoms.143144

CDC and others recommend IV quinidine gluconate regimen be administered in an intensive care facility with close monitoring.111122123124125126134141143153

Because most deaths from severe malaria occur within first 24–48 hours of illness, an initial IV loading dose usually used to rapidly provide therapeutic plasma concentrations.143144 Do not use a loading dose if patient received >40 mg/kg of quinine in the previous 48 hours or received mefloquine in the previous 12 hours.143

Calculate loading dose and infusion rate carefully to prevent acute cardiac events.153 Consider that risk of serious ventricular arrhythmias associated with quinidine is increased by bradycardia, hypokalemia, hypomagnesemia, and concomitant use of drugs that can prolong QT interval (e.g., halofantrine [an antimalarial drug not commercially available in US], mefloquine, quinine).134143153

CDC recommends consultation with a cardiologist and a clinician with experience in treating malaria.143144153 A cardiologist may be helpful if attempting to resume IV infusion of quinidine gluconate in patients who develop prolongation of QT interval or hypotension during treatment.153

Oral Administration

May be administered with food or antacids to decrease adverse GI effects.b Avoid grapefruit juice.156163168169 (See Specific Drugs and Foods under Interactions.)

To determine possible idiosyncrasy to quinidine, administer a test dose of 200 mg of quinidine sulfate orally several hours before initiating full dosage.b For children, the test dose for idiosyncrasy is 2 mg/kg (up to 200 mg) of quinidine sulfate orally.164b

Extended-release Tablets

Used principally for maintenance therapy in the management of arrhythmias.b

Quinidine gluconate extended-release tablets may be broken in half in order to titrate dosage; however, do not chew or crush.168169

IV Administration

For solution and drug compatibility, see Compatibility under Stability.

Dosage

Available as quinidine sulfate163167170 and quinidine gluconate.119168169 Dosage for treatment of arrhythmias usually expressed in terms of the salt;119163167168169170 dosage for treatment of malaria expressed in terms of the base or salt.119143144

On a molar basis, approximately 267 mg of quinidine gluconate is equivalent to 200 mg of quinidine sulfate.b

Pediatric Patients

Quinidine Sulfate

15–60 mg/kg of quinidine sulfate daily given in divided doses every 6 hours has been recommended by some clinicians.164165 Others recommend 30 mg/kg daily or 900 mg/m2 daily, given in 5 divided doses.b

Quinidine Gluconate

20–60 mg/kg of quinidine gluconate daily given in divided doses every 8 hours has been recommended by some clinicians.165

IV

30 mg/kg daily or 900 mg/m2 daily of quinidine gluconate, given in 5 divided doses, is recommended by some clinicians.b

Severe Malaria

IV

Continuous IV infusion regimen: Initial loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate) given by IV infusion over 1–2 hours,119134143144 followed by a maintenance infusion of 12.5 mcg/kg of quinidine per minute (20 mcg/kg of quinidine gluconate per minute) continued for ≥24 hours and until parasitemia is reduced to <1% and oral quinine sulfate can be substituted.111119122123124125134141143144 Some clinicians state initial loading dose should not exceed 375 mg of quinidine (600 mg of quinidine gluconate).134

Intermittent IV infusion regimen: Initial loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate) given by IV infusion over 4 hours, followed 4 hours later (i.e., 8 hours after the beginning of the loading-dose infusion) by maintenance doses of 7.5 mg/kg of quinidine (12 mg/kg of quinidine gluconate) given by IV infusion over 4 hours at 8-hour intervals until 3 maintenance doses have been administered and parasitemia is reduced to <1% and oral quinine sulfate can be substituted.119143144153

After ≥24 hours of quinidine gluconate and when clinically indicated, switch to oral quinine sulfate therapy to complete a total of 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).122123141143144

IV quinidine gluconate regimen followed by oral quinine sulfate is used in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (given IV or orally as tolerated).143

Adults

Quinidine Sulfate

Arrhythmias

Oral

Conversion of atrial fibrillation/flutter (conventional tablets): Manufacturers recommend 400 mg of quinidine sulfate (332 mg of quinidine) every 6 hours initially; dose may be cautiously increased if conversion is not attained after 4 or 5 doses.167170

Conversion of atrial fibrillation/flutter (extended-release tablets): Manufacturer recommends 300 mg of quinidine sulfate (249 mg of quinidine) every 8–12 hours initially; dose may be cautiously increased if conversion not attained, quinidine serum concentrations are within the therapeutic range, and the drug is well tolerated.163

If successful conversion of atrial fibrillation does not occur when quinidine serum concentrations are in the therapeutic range, further dosage increases generally are unsuccessful and increase the possibility of toxicity.b

Reduction in frequency of relapse into atrial fibrillation/flutter (conventional tablets): Manufacturers recommend 200 mg of quinidine sulfate (166 mg of quinidine) every 6 hours initially.167170 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.167170 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;167170 consider mortality risk.167170

Reduction in frequency of relapse into atrial fibrillation/flutter (extended-release tablets): Manufacturer recommends 300 mg of quinidine sulfate (249 mg of quinidine) every 8–12 hours initially.163 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.163 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;163 consider mortality risk.163

Manufacturers state that dosage regimens for suppression of life-threatening ventricular arrhythmias have not been adequately studied, but regimens similar to those used in the management of atrial fibrillation/flutter have been described.163167170 Whenever possible, such therapy should be guided by results of programmed electrical stimulation and/or Holter monitoring with exercise.163167170

Malaria

Oral

300–600 mg or 10 mg/kg of quinidine sulfate every 8 hours for 5–7 days has been used for treatment of uncomplicated P. falciparum malaria.102103108109110

Not included in CDC recommendations for treatment of uncomplicated or severe malaria.143144 (See Malaria under Uses.)

Quinidine Gluconate

Arrhythmias

Oral

Conversion of atrial fibrillation/flutter (extended-release tablets): Manufacturers recommend 648 mg of quinidine gluconate (403 mg of quinidine) every 8 hours initially; dose may be cautiously increased if conversion is not attained after 3 or 4 doses.168169 Alternatively, manufacturers state that a regimen of 324 mg of quinidine gluconate (202 mg of quinidine) may be given every 8 hours for 2 days, then 648 mg of quinidine gluconate (403 mg of quinidine) every 12 hours for 2 days, and then 648 mg of quinidine gluconate (403 mg of quinidine) every 8 hours for up to 4 days.168169 If the 648-mg dose is not tolerated, the lower dosage can be continued for the last 4 days.168169

Reduction in frequency of relapse into atrial fibrillation/flutter (extended-release tablets): Manufacturers recommend 324 mg of quinidine gluconate (202 mg of quinidine) every 8 or 12 hours initially.168169 Dose may be cautiously increased if well tolerated, serum quinidine concentrations are within therapeutic range, and average time between arrhythmic episodes has not been satisfactorily increased.168169 Use such prophylaxis only if alternative measures have been inadequate and if potential benefits outweigh risks;168169 consider mortality risk.168169

Manufacturers state that dosage regimens for suppression of life-threatening ventricular arrhythmias have not been adequately studied, but regimens similar to those used in the management of atrial fibrillation/flutter have been described.168169 Whenever possible, such therapy should be guided by results of programmed electrical stimulation and/or Holter monitoring with exercise.168169

IV

Treatment of symptomatic atrial fibrillation/flutter: Initially, up to 0.25 mg/kg of quinidine gluconate per minute (i.e., up to 1 mL/kg per hour) of 16-mg/mL dilution.119 Discontinue IV infusion as soon as sinus rhythm is restored.119

Most arrhythmias responsive to IV quinidine respond to a total IV dosage <5 mg/kg, although 10 mg/kg may be required in some patients.119 If conversion to sinus rhythm has not occurred after infusion of quinidine gluconate 10 mg/kg, discontinue the infusion and consider other means of cardioversion.119

Although dosing regimens for the management of life-threatening ventricular arrhythmias have not been systematically evaluated, regimens similar to that used in the management of atrial fibrillation/flutter have been described.119

Severe Malaria

IV

Continuous IV infusion regimen: Initial loading dose of 6.25 mg/kg of quinidine (10 mg/kg of quinidine gluconate) given by IV infusion over 1–2 hours,119134141143144 followed by a maintenance infusion of 12.5 mcg/kg of quinidine per minute (20 mcg/kg of quinidine gluconate per minute) continued for ≥24 hours and until parasitemia is reduced to <1% and oral quinine sulfate can be substituted.111119122123124125134141143144 Some clinicians state initial loading dose should not exceed 375 mg of quinidine (600 mg of quinidine gluconate).134

Intermittent IV infusion regimen: Initial loading dose of 15 mg/kg of quinidine (24 mg/kg of quinidine gluconate) given by IV infusion over 4 hours, followed 4 hours later (i.e., 8 hours after the beginning of the loading-dose infusion) by maintenance doses of 7.5 mg/kg of quinidine (12 mg/kg of quinidine gluconate) given by IV infusion over 4 hours at 8-hour intervals until 3 maintenance doses have been administered and parasitemia is reduced to <1% and oral quinine sulfate can be substituted.119143144153

After ≥24 hours of quinidine gluconate and when clinically indicated, switch to oral quinine sulfate therapy to complete a total of 7 or 3 days of total quinidine and quinine therapy as determined by geographic origin of infecting parasite (7 days if acquired in Southeast Asia or 3 days if acquired elsewhere).122123141143144

IV quinidine gluconate regimen followed by oral quinine sulfate is used in conjunction with a 7-day regimen of doxycycline, tetracycline, or clindamycin (given IV or orally as tolerated).143144

Special Populations

Hepatic Impairment

Renal Impairment

In patients with severe malaria receiving IV quinidine gluconate, CDC states that initial (including loading) doses do not need to be reduced in those with renal failure.143 If renal failure persists or clinical improvement does not occur in such patients, CDC recommends reducing maintenance IV infusion rate by one-third to one-half on the third day of treatment.143

CHF

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosage range, and consider age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.119

Cautions for Quinidine Gluconate

Contraindications

Patients with AV junctional or idioventricular pacemaker, including those in complete AV block.119163167168169170

Warnings/Precautions

Warnings

Mortality

Pooled analysis of data from several randomized, controlled studies in patients with ventricular arrhythmias indicates that mortality rate associated with quinidine therapy is at least as high as that associated with other antiarrhythmic agents (e.g., flecainide, mexiletine, propafenone, tocainide).b

Use quinidine only for life-threatening arrhythmias.145 Avoid use for less severe ventricular arrhythmias and treatment of asymptomatic VPCs.145

Additionally, pooled analysis of data from several randomized, controlled studies in patients with atrial flutter and fibrillation indicates that quinidine therapy may be associated with a mortality rate >3 times higher than that associated with placebo;163167168169170 consider the increased risk of death when initiating quinidine therapy.149

Use with extreme caution, if at all, in patients with incomplete AV nodal block, since complete heart block and asystole may result.b Parenteral administration is especially hazardous in the presence of AV block, in the absence of atrial activity, and in patients with extensive myocardial injury.b

Proarrhythmic Effects

The possibility that potentially serious cardiac arrhythmias, including torsades de pointes, could occur if used concomitantly with other drugs that prolong the QTc interval should be considered.119

Hypokalemia, hypoxia, and disorders of acid-base balance must be eliminated as potentiating factors in patients who require large doses of antiarrhythmic agents to control ventricular arrhythmias.b

Paradoxically, an extremely rapid ventricular rate may occur when used in the treatment of atrial flutter or fibrillation, due to a reduction in the degree of AV nodal block to a 1:1 ratio.b The anticholinergic action on the AV node also may increase the heart rate.b

Exacerbated Bradycardia in Sick Sinus Syndrome

IV Administration

Sensitivity Reactions

Hypersensitivity Reactions

Idiosyncratic and hypersensitivity reactions to quinidine may occur, and the reaction to a test dose or the first dose of the drug should be observed carefully.b (See Oral Administration under Dosage and Administration.)

General Precautions

Cardiovascular Effects

Possible syncope, probably due to ventricular tachycardia or fibrillation in usual doses.b Syncopal episodes may subside spontaneously, but occasionally are fatal.b If quinidine-induced syncope occurs, discontinue the drug.b Also may cause bradycardia.b

Severe hypotension may occur following IV administration or oral overdosage.b Vascular collapse, respiratory distress, and respiratory arrest may occur.b Reportedly related to the dose and rate of administration of the drug.102107119 Rapid IV injection of as little as 200 mg reportedly may cause a decrease in blood pressure of 40–50 mm Hg.119 Norepinephrine or metaraminol may be used if necessary to treat vascular collapse; artificial respiration and other supportive measures may be required.b

Availability for Use in Treatment of Severe Malaria

Because of potentially fatal consequences of delays in initiating treatment of severe malaria, institutional pharmacy services should be aware of the essential role of ready availability of IV quinidine gluconate.b142143148153

If IV quinidine gluconate is not readily available for a patient with severe P. falciparum malaria (e.g., in hospitals where the drug is not maintained on formulary or otherwise available), health-care professionals should contact a nearby healthcare facility that stocks the drug.143 If a local source cannot be found, contact local or regional distributor or manufacturer of the drug.143

If IV quinidine gluconate is unavailable locally and cannot be obtained quickly or cannot be used because of adverse effects or contraindications or if parasitemia is high and has not responded to quinidine gluconate, IV artesunate is available from CDC under an IND protocol for initial treatment of severe malaria.143144171172 (See Malaria under Uses.)

Lactation

Pediatric Use

Safety and efficacy as an antiarrhythmic agent in children not established.119163167168169170 Has been used in children with arrhythmias†.165b

Study and experience in children with malaria suggest that safety and efficacy of IV quinidine gluconate are similar to those in adults.119

Geriatric Use

Safety and efficacy not systematically studied in geriatric patients.119167168169170 Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger adults;119 other reported clinical experience has not identified differences in responses between geriatric adults and younger patients.119

When used in geriatric patients, select dosage with caution, usually initiating therapy at the low end of dosage range, and consider the greater frequency of decreased hepatic, renal, and/or cardiac function and concomitant disease and drug therapy in this age group.119

Drugs or Foods Affecting or Metabolized by Hepatic Microsomal Enzymes

Possible pharmacokinetic interactions with drugs that are inhibitors, inducers, or substrates of CYP3A4.119163167168169170

Use caution if drugs metabolized by CYP2D6 (e.g., mexiletine, some phenothiazines, polycyclic antidepressants) are used concomitantly with quinidine;119163167168169170 reduced dosage of such drugs may be necessary to obtain clinical benefit without toxicity.119163167168169170 If some prodrugs that require CYP2D6 for conversion to an active metabolite (e.g., codeine, hydrocodone) are used concomitantly with quinidine, it may not be possible to achieve desired clinical benefits of those drugs.119163167168169170

Propranolol: Usually does not affect quinidine pharmacokinetics, but increased peak quinidine concentrations and decreased volume of distribution and decreased clearance has been reported;119 no clinically important effect on propranolol pharmacokinetics119163167168169170

Flecainide, metoprolol, propafenone: Quinidine has no clinically important effect on pharmacokinetics of these antiarrhythmics119163167168169170

If quinidine and clarithromycin are used concomitantly, monitor ECGs and serum quinidine concentrations159

Dextromethorphan

Substantial increase in bioavailability of dextromethorphan due to CYP2D6 inhibition; used for therapeutic benefit in fixed combination containing dextromethorphan and quinidine (Nuedexta)174

Digoxin

Increased plasma concentrations of digoxin119163167168169170b (in ≥90% of patients) which may result in GI and cardiac toxicity;b no clinically important effect on quinidine pharmacokinetics119163167168169170

Distribution

Extent

Plasma Protein Binding

About 80–88% bound to plasma proteins in adults and older children;119163167168169170 lower protein binding in pregnant women, infants, and neonates (may be as low as 50–70% in neonates and infants).119163167168169170

Possesses anticholinergic properties that may modify the direct myocardial effects of the drug.b

The exact mechanism has not been determined conclusively, but is believed to combine with fast sodium channels in their inactive state and thereby inhibit recovery after repolarization in a time- and voltage-dependent manner, which is associated with subsequent dissociation of the drug from the sodium channels.b

Suppresses automaticity in the His-Purkinje system.b Decreases conduction velocity in the atria, ventricles, and His-Purkinje system, and may decrease or cause no change in conduction velocity through the AV node.

May suppress atrial fibrillation or flutter by prolonging the effective refractory period (ERP) and increasing the action potential duration in atrial and ventricular muscle and in the His-Purkinje system.b

Has a direct negative inotropic effect, but therapeutic plasma concentrations of the drug do not usually depress contractility in the normal heart.b

May reduce peripheral resistance and blood pressure by blockade of α-adrenergic receptors and by its effects on myocardial contractility; decreased blood pressure is most likely to occur with high plasma concentrations of the drug.b At high plasma concentrations, quinidine may produce sinus tachycardia because of reflex sympathetic response to the drug’s hypotensive effect.b

When used as an antimalarial agent, acts principally as an intraerythrocytic schizonticide; the drug has little effect on sporozoites or preerythrocytic parasites.119

Gametocidal against Plasmodium vivax and P. malariae, but not P. falciparum.119

Appears to be more active (in vitro on a weight basis) than quinine against P. falciparum.102103104112

Advice to Patients

If used for prophylaxis against recurrence of atrial fibrillation, advise patient of the risks and benefits.163167168169170 Advise patients that the goal is reduction in frequency of episodes of atrial fibrillation (probably not elimination); symptomatic benefits may occur if reduced frequency of fibrillatory episodes is achieved; no data indicate that reduced frequency of fibrillatory episodes reduces risks of irreversible harm through stroke or death; and data are available suggesting that quinidine treatment is likely to increase the risk of death.163167168169170

Importance of informing clinician if rash, fever, unusual bleeding or bruising, ringing in the ears, or visual disturbance occurs.b

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.119163167168169170

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.119163167168169170

Importance of informing patients of other important precautionary information.119163167168169170 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

144. Centers for Disease Control and Prevention. Guidelines for treatment of malaria in the United States (based on drugs currently available for use in the United States–updated July 1, 2013). From the CDC website. Accessed 2013 Sep 27. http://www.cdc.gov/malaria

161. World Health Organization (WHO). Guidelines for the treatment of malaria. 2nd edition. Geneva, Switzerland: World Health Organization; 2010. Updates may be available at WHO website. http://www.who.int/malaria/publications/atoz/9789241547925/en/index.html

171. Centers for Disease Control and Prevention. Notice to readers: new medication for severe malaria available under an investigational new drug protocol. MMWR Morb Mortal Wkly Rep. 2007; 56:769-70.

172. Centers for Disease Control and Prevention. Artesunate is available to treat severe malaria in the United States. From CDC website. Accessed 2014 Jun 2. http://www.cdc.gov/malaria/diagnosis_treatment/artesunate.html